Laboratory studies suggest that it may be possible for insects to overcome two disparate toxins produced by genetically modified cotton. The results strike a cautionary note at a time when developers are racing to create crops that produce many different pesticides.

Insects can become resistant to individual insecticides in much the same way as bacteria develop resistance to antibiotics. One way to reduce this threat is to adopt a 'pyramid' approach and create crops that produce multiple toxins that target the same pest.

"This is the current trend of all the companies," says Juan Ferré, a geneticist at the University of Valencia in Spain. "They are all combining more than one gene to have better control and to delay resistance." For example, next year, Monsanto, a US agricultural products company based in St Louis, Missouri, intends to launch a line of maize (corn) that contains eight different genes that make the crop resistant to herbicides and to attack by insects.

[quote: "Evolution by insects is not something that scientists are going to stop." - Bruce Tabashnik, University of Arizona]

One of the most common 'pyramided' crops on the market is cotton that produces two different 'Bt' toxins made naturally by the bacterium Bacillus thuringensis. The two toxic proteins, Cry1Ac and Cry2Ab, have very different amino-acid sequences and bind to different target sites.

As a result, mutations that confer resistance to both toxins were thought to be unlikely, says Bruce Tabashnik, an entomologist at the University of Arizona in Tucson. "The main way that insects become resistant is by altering the binding site of the toxin," he says. "These two toxins don't bind to the same site - if the insects altered the Cry1Ac binding site, it's not going to give cross resistance to Cry2Ab."

But when Tabashnik and his colleagues tried to selectively breed insects that were resistant to Cry2Ab, they found that that some were also resistant to Cry1Ac. The results are reported this week in Proceedings of the National Academy of Sciences1.

Arms race

The researchers were studying pink bollworm (Pectinophora gossypiella) ”” a particular nuisance in the cotton fields of the southern United States. Crops expressing Cry1Ac have thus far largely held the pest at bay, and there has been no sign of Cry1Ac resistance emerging in the insects.

Tabashnik wanted to learn more about how insects may become resistant to the less-studied Cry2Ab protein, so the team raised a number of different laboratory strains of pink bollworms on a diet that contained the toxin. To their surprise, they generated a strain of pink bollworm that was not only resistant to 240-times higher levels of Cry2Ab than normal, but also to 420-times higher concentrations of Cry1Ac.

Although the binding sites of the two toxins differ, both toxins are activated via the same pathway in the insect. A change in the protease responsible for activating the toxins could provide an avenue to cross-resistance, Tabashnik says. Other changes in the insect's ability to cope with damaged cells could also play a part, says Ferré, who was not involved with the study.

The results show that cross-resistance between the two toxins is possible. But "this does not pose a threat for control by the current pyramided Bt cotton of this insect", Tabashnik says. The resistant pink bollworms were able to withstand high concentrations of both toxins in their diets, but they were not able to survive the higher concentrations of Cry2Ab found on cotton bolls produced by the pyramided transgenic cotton.

Ferré urges caution on extrapolating laboratory results to the field. "This is a special condition in the laboratory," he says. "The important thing is to find out whether that resistance can be obtained in the field."

Nevertheless, the results do highlight the continued threat of resistance, adds Tabashnik. "Pyramids are not a panacea," he says. "Evolution by insects is not something that scientists are going to stop."